tbuckley/cabot-search huggingface dataset:
Demographic and socioeconomic factors in poorly differentiated Sertoli-Leydig cell tumors: A National Cancer Database analysis.
Authors: Laura Cogua
Journal: Journal of Clinical Oncology (2023)

e17568 Background: Poorly differentiated Sertoli-Leydig cell tumor (PD-SLCT) is a rare and aggressive type of ovarian cancer. This cancer has a 5-year cancer-specific survival rate of 43.9% with a chance of early relapse of approximately 2-3 years following initial diagnosis. Given the rarity of the cancer, potential risk factors could offer providers and patients more information about the epidemiology. The National Cancer Database (NCDB) was analyzed to study the demographic factors in patients diagnosed with PD-SLCT. Methods: Cases of PD-SLCT (N = 405) in the NCDB from 2004 – 2020 were determined via histology (ICD-O-3 code = 8631). A retrospective cohort analysis using demographic factors such as race, age, sex, insurance status, urban/rural, facility type, and Charleson-Deyo score were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: A total of 405 patients with a diagnosis of PD-SLCT were identified in the database with a steady incidence of patients diagnosed per year (mean = 23.8 per year, R2 = 0.1). The average age of diagnosis was 41.7 years (SD = 20.1, range = 8 – 90 years). The majority of patients were non-Hispanic (82.5%) and White (69.4 %). More patients were in the top quartile of income earners (30.8.%) and were privately insured (56.8%) relative to those who were uninsured or insured by Medicare/Medicaid (43.2%). A greater percentage of patients with PD-SLCT were treated at a non-academic program (54.0%) compared to an academic/research program (46.0%). More patients lived in metropolitan counties with a population greater than 1 million (59.8%) versus less populated metropolitan communities or urban communities (40.2%). Most individuals (84.2%) had Charlson-Deyo comorbidity scores of 0. Conclusions: This novel study of the NCDB addresses a significant knowledge gap on patients with PD-SLCT, as it provides demographic insight into this rare type of tumor and the patients who are diagnosed with it. Most PD-SLCT patients tend to be in the premenopausal age, as previously described in literature. Most patients are White and non-Hispanic. This is the first time the socioeconomic factors of PD-SLCT patients have been described in the literature: patients are more likely to be in the top income quartile, live in densely populated metropolitan areas, and be treated in a non-academic program. Further research is needed to better understand the impact of these factors on the diagnosis of, treatments utilized, and overall survival of patients with PD-SLCT to ensure that all patients receive the best possible care, regardless of their background.
Landmark analysis of OS by response status in previously treated patients (pts) with advanced hepatocellular carcinoma (aHCC): Post hoc analysis of the KEYNOTE-394 study.
Authors: Zhenggang Ren, Zhendong Chen, Weijia Fang, Shuangyan Ou, Baek-Yeol Ryoo, Zhiqiang Meng, Yuxian Bai, Xiaoming Chen, Xiufeng Liu, Juxiang Xiao, Gwo Fuang Ho, Yimin Mao, Xin Wang, Ying Jieer, Chunyi Hao, Hujia Shen, Jianxin Lin, Ken Hatogai, Abby B. Siegel, Shukui Qin
Journal: Journal of Clinical Oncology (2023)

4074 Background: KEYNOTE-224 and KEYNOTE-240 landmark analyses showed that objective response (OR) in pembrolizumab (pembro)-treated pts was prognostic of longer OS after the landmark. Landmark analysis was performed using the KEYNOTE-394 study to determine whether response assessment before landmark is prognostic of longer OS after landmark time in pembro-treated pts. Methods: Adults with confirmed HCC, radiographic progression during or after treatment with or intolerance to sorafenib or oxaliplatin-based chemotherapy were eligible for KEYNOTE-394. Landmark analyses of OS for responders, pts with SD, and pts with other status in these analyses at 6, 12, 18, and 24 wk after randomization were performed on the pembro arm. Tumor imaging was performed every 6 wk after randomization. Responders (R) at each landmark were defined as pts with any response assessment of CR or PR before the landmark date; all other pts were defined as nonresponders (NR). SD at each landmark was defined as pts with a response assessment of SD and no better response before the landmark date. Other was defined as pts with responses of PD or a missing/not evaluable status. Response was assessed per RECIST v1.1 by blinded independent central review. HR and 95% CI for survival after the landmark are based on the Cox regression model with the Efron method for handling ties, with response status by the landmark time as a single covariate. Results: Median time from randomization to data cutoff date (June 30, 2021) was 33.8 mo (range, 18.7-48.8) for pembro. OS after landmark time was numerically longer for R vs NR, R vs pts with SD, and pts with SD vs pts with Other status. Conclusions: KEYNOTE-394 landmark analysis supports the prognostic association between OR with pembro before the landmark and OS after the landmark observed in KEYNOTE-224 and KEYNOTE-240 in previously treated pts with aHCC. Landmark analysis also suggested longer OS after the landmark for pts who achieved a better response to pembro before the landmark. Clinical trial information: NCT03062358 . [Table: see text]
Cost-effectiveness analysis of later-line therapies for metastatic colorectal cancer (mCRC) based on a novel methodology of network meta-analysis (NMA) of survival curves.
Authors: Mavis Obeng-Kusi, Denise Roe, Brian L Erstad, Ivo Abraham
Journal: Journal of Clinical Oncology (2023)

3605 Background: With advances in the management of mCRC, survival outcomes of patients have improved. While some patients still progress after first and second lines of treatment, there remain options for third or later-line treatment. This study aimed to determine the cost-effectiveness of later-line (&gt;3) treatments for patients with mCRC in the US, based on a NMA of survival curves. Unlike conventional NMA using constant hazard ratios, this method is not constrained by the proportional hazard assumption and uses parametric fitting that incorporates the shape and scale parameters to provide time-varying treatment effects. Methods: The NMA compared the efficacy of 6 treatments, atezolizumab+/-cobimetinib (ATE+/-COB), fruquintinib (FRU), regorafenib (REG), TAS-102+/-bevacizumab (TAS+/-BEV), including biosimilar, to placebo (PBO). The study used a 3-state partitioned survival model over a 5-year time horizon incorporating drug acquisition, administration, adverse events, monitoring, and end of life costs, and utilities sourced from literature. Total costs, life-years (LY) and quality-adjusted LYs (QALY) for each treatment were determined. Incremental cost-effectiveness (ICER) and incremental cost-utility ratios (ICUR) were estimated using PBO as a common comparator. Results: Over the 5-year period and across the 6 therapies, survival ranged from 0.62 LYs for PBO to 1.15 LYs for TAS+BEV, translating to QALYs ranging from 0.44 for PBO to 0.85 for TAS+BEV. Total costs of treatment ranged from 278,877 for PBO to 417,495 for TAS+BEV (405,002 with biosimilar). TAS+BEV yielded the lowest ICER of an additional 261,421 (237,860 with biosimilar)/LY gained (g) and ICUR of an additional 343,458 (312,504 with biosimilar)/QALYg; while ATE presented the least favorable ICER and ICUR of an additional $522,602/LYg and $701,381/QALYg, respectively (Table). Conclusions: Among the 6 treatments evaluated, TAS+BEV emerged as the most cost-effective later-line treatment for mCRC while atezolizumab was the least cost-effective. Additionally, replacing BEV with a biosimilar reduces costs and enhances cost-effectiveness, improving access for patients. [Table: see text]
Induction chemotherapy with nanosomal docetaxel lipid suspension (NDLS), cisplatin, and fluorouracil in patients with locally advanced head and neck squamous cell carcinoma.
Authors: Ghanashyam Biswas, Ranga Raman Ganta, Kharthik N, Rajesh Kantharia, Shailesh Bondarde, Ramaiyer Raghu Raman, Manoj Mahajan, Ateeq Ahmad, Saifuddin Sheikh, Shoukath M Ali, Mahesh Paithankar, Lav Patel, Anil Rajani, Deepak Bunger, Alok Chaturvedi, Imran Ahmad
Journal: Journal of Clinical Oncology (2023)

6074 Background: Nanosomal docetaxel lipid suspension (NDLS), a polysorbate-80 and ethanol free formulation, was developed to overcome the toxicity issues and to improve disease outcomes associated with conventional docetaxel. We evaluated the safety and efficacy of NDLS based TPF (NDLS, cisplatin and 5-fluorouracil [FU]) induction chemotherapy in patients with inoperable/unresectable Locally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC). Methods: In this multicentric, single arm, open label, Phase IV clinical study, patients with inoperable/ unresectable LA HNSCC received induction chemotherapy with NDLS (75 mg/m 2 ; Day 1), cisplatin (75 mg/m 2 ; Day 1) and 5-FU (750 mg/m 2 /day for 5 days) based TPF regimen every 3 weeks (q3w) for 4 cycles followed by radiotherapy. The study outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: Fifty patients were enrolled in this study. Most of the patients belonged to the age group of 35-64 years (86%) and had a WHO performance status of 1 (66%). In the modified intent-to-treat (mITT) population ( n = 40), the ORR after NDLS based TPF induction chemotherapy was 42.5%, which increased to 60.0% after loco-regional therapy. In the per-protocol (PP) population ( n = 14), the ORR was 64.3%, which increased to 80.0% after loco-regional therapy (Table). At 2 years, the PFS and OS rates were 82.5% and 97.5%, respectively, in the mITT population and 85.7% and 100% respectively, in the PP population. The most common grade 3/4 adverse effects reported were neutropenia (10%), leukopenia (6%), febrile neutropenia (4%), asthenia (2%), diarrhea (2%), and thrombocytopenia (2%) respectively. Grade 3/4 infusion-related reactions, hyperglycemia or neuropathy were not reported. Conclusions: NDLS based induction chemotherapy was effective and well-tolerated in the treatment of inoperable LA HNSCC and showed high response rates. Clinical trial information: CTRI/2017/12/010938 .[Table: see text]
RT-PACE: Phase I/II study of adjuvant whole pelvic hypofractionated radiotherapy for non-metastatic cervical and endometrial cancer.
Authors: Christina H. Son, Gita Suneja, Jonathan Chipman, John Cursio, Hania A Al-Hallaq, David K. Gaffney, Yasmin Hasan
Journal: Journal of Clinical Oncology (2023)

TPS5631 Background: Whole pelvic radiation therapy (WPRT) improves locoregional control in women with high-intermediate and high-risk endometrial cancer. The standard treatment course consists of 25-28 fractions (5-5.5 weeks) of 1.8-2 Gy/fraction, and is delivered using intensity-modulated radiation therapy (IMRT), which allows for superior sparing of normal tissue with a subsequent lower rate of acute and late toxicity compared to less conformal treatment techniques. Moderate hypofractionation (HF, &gt;2 Gy/fraction) has been studied in other disease sites, such as breast and prostate cancer, and is associated with lower or comparable toxicity, improved patient convenience, and greater cost savings compared to standard fractionation. However, HF has not been well-studied in the setting of WPRT for gynecologic cancers. Methods: This phase I/II multi-institutional study evaluates the feasibility, safety, and toxicity profile of HF-WPRT in women with non-metastatic cervical or endometrial cancers who have undergone curative hysterectomy and are recommended adjuvant WPRT by their treating physician. Concurrent chemotherapy is not allowed, but can be administered sequentially prior to or after WPRT. Para-aortic radiation or nodal boosts are not allowed, however vaginal brachytherapy boost is permissible. Phase I is a safety study of increasing dose-per-fraction. All treatment regimens have an approximate biologic effective dose of 53 Gy (α/β =10). A keyboard design is utilized to identify the maximum tolerated dose-per-fraction (MTD), defined in this study as the regimen that is associated with a CTCAE grade 3+ gastrointestinal/genitourinary toxicity rate of ≤10% on the last day of WPRT. There are 3 dose cohorts of increasing dose-per-fraction. Phase II will accrue 64 evaluable patients to HF-WPRT using the MTD determined in phase I. The primary endpoint is to evaluate the change in patient-reported gastrointestinal toxicity from baseline to the last day of WPRT using the EPIC bowel score. The study is powered to compare results to the RTOG 1203 IMRT standard fractionation arm. The phase 1 portion of the study completed accrual; the phase II portion opened in April 2022 with a fractionation of 42.56 Gy in 16 fractions. Secondary endpoints include genitourinary toxicity (EPIC, CTCAE), quality of life (FACT-Cx, PRO-CTCAE), financial toxicity (FACIT-COST), and decision-making (Decision Regret Scale). Pelvic control at 2 years is an exploratory endpoint. Clinical trial information: NCT04683653 .
Progression-free survival in patients receiving first-line platinum-based therapy in Argentina: OCEANIA study.
Authors: Gabriela Abreu, Juliana Queiroz, Thiago Nogueira, Claudia Soares, Patricia Menezes, Mariano Nicolas Carrizo, Juan Criniti, Rosana Felice, Paula Scibona, Ventura Simonovich, Maria Cecilia Riggi, Florencia Cravero, Diego Odetto, José Saadi, Laura Fabia Jotimliansky
Journal: Journal of Clinical Oncology (2023)

e17593 Background: OCEANIA is a retrospective database study that evaluated treatment patterns and outcomes in a cohort of patients diagnosed with all ovarian cancer (OC) types in private healthcare settings in Brazil and Argentina. The present analysis described up to 5-year real-world (RW) outcomes in an OC cohort of patients who received first-line platinum-based treatment (PBT) in Argentina. Methods: Patients with an OC code diagnosed from 2010 to 2019 who received a PBT alone or in combination with other therapeutic modalities (other antineoplastics, surgery, and/or radiotherapy) were selected from a private healthcare provider’s database (Hospital Italiano de Buenos Aires) in Argentina. Frequency of PBT patients by FIGO (International Federation of Gynecology and Obstetrics) stage was described. Cumulative risk of progression to subsequent treatment or death was calculated for one year up to five years after the end of first PBT from the survival analysis (using Kaplan–Meier analyses). RW progression-free survival (RW-PFS) was defined as the time between the end of first PBT and the beginning of subsequent treatment or death; patients who were lost to follow-up were censored at the end of the study period. Results: From 741 OC patients in the database, 321 (43.3%) were exposed to a PBT. Among this population, 89.4% had information about FIGO staging: 39 (13.6%) were stage 1; 23 (8.0%) stage 2; 195 (67.9%) stage 3; and 30 (10.5%) stage 4. During the follow-up period, 209 events were recorded, including 181 progressions to subsequent treatments and 28 deaths. The unadjusted mean (standard deviation) and median RW-PFS were 16 (22.3) months and 6 months, respectively. The adjusted cumulative risks of progression or death for years 1–5 were 53.8%, 67.6%, 71.2%, 74.4%, and 76.1%, respectively. Conclusions: Almost two thirds (65.1%) of patients with OC exposed to PBT progressed to subsequent treatment or death during follow-up. The greatest risk of progression was observed within the first year after end of PBT, likely because almost 80% of patients were at stages 3 and 4 and the therapeutic options available during the study period were limited. Funding: GSK213815.
Novel use of alternate (Alt) response (Rp) criteria (Cr) for early prediction of outcomes in pancreatic (P) neuroendocrine tumors (NETs): Utilizing banked imaging data from the ECOG-ACRIN E2211 study.
Authors: Namrata Vijayvergia, Elizabeth A. Handorf, Pamela L. Kunz, Emel Alkim, Lauren M.B. Burke, Paul J. Catalano, Noah Graham, Laura Levin, Weier Li, Caitlin R. Meeker, Daniel L Rubin, Anush Narasimhan Sridharan, Peter J. O'Dwyer, Terence Z. Wong, Jordan Anaokar
Journal: Journal of Clinical Oncology (2023)

4133 Background: The evaluation of treatment (Tx) Rp in NETs using CT/MRI scans can be difficult. Previous studies, including the E2211, have shown improved progression-free survival (PFS) but no significant difference in Rp as measured by RECIST 1.1 (R1.1) Cr. Thus, making it difficult to determine Tx effectiveness with short-term imaging, further complicated by differences in imaging protocols and inter-reader variability. Incorporating tumor density, using smaller threshold changes in tumor size, and novel quantitative features may be more sensitive and precise than R1.1 (e.g. CHOI in GIST) but they have not been studied for NETs. Methods: Banked CT images from the E2211 trial were repurposed to study novel Cr. Three radiologists provided a R1.1 assessment. Density and radiomic features were calculated from a 2D region of interest in the portal venous phase (as per CHOI Cr). Patients were classified as responders (PR), stable disease (SD), or progressive disease (PD) based on R1.1 and CHOI and compared with PFS to determine the best predictor. Radiomic features were analyzed using pyradiomics. Wilcoxon tests were used to compare scan quality by center type, agreement was measured using Cohen’s Kappa, and predictive value was quantified using the c-statistic and AUC for time-varying outcomes. Results: 67 patients had their scans repurposed for the study. Inter-reader agreement for overall imaging studies was fair, with only 5 of 9 PD cases noted by reviewer 1 being agreed upon by reviewer 2 (proportional agreement for PD = 0.56) and a Kappa of 0.6 (95% CI 0.41 – 0.79). The CHOI Cr showed improved prediction of PFS compared to R1.1 (12-month AUC 0.75 for CHOI vs 0.69 for R1.1, c-statistic 0.66 vs 0.64, p=0.22), and was able to predict improved PFS for PR versus SD at the first interval scan. This was not seen with R1.1 (table). Radiomics and texture analysis as a potential adjunct to CHOI is being studied and results will be presented. Conclusions: This study using repurposed banked imaging from an NCTN trial, found that there was significant variability in the interpretation of images, and that the R1.1 Cr had a poor correlation with Rp in PNETs. The CHOI Cr emerged as a better alternative as it may have a better correlation with PFS and the ability to predict outcomes at the point of first disease assessment. Importantly, CHOI Cr can be easily applied in clinical practice to inform treatment decisions. Further research is needed to confirm these findings and define the therapeutic importance. [Table: see text]
Donafenib combined with anti-PD-1 antibody as adjuvant treatment in patients with hepatocellular carcinoma at high risk of recurrence after radical resection: A retrospective analysis.
Authors: Chenggang Li, Hanchuan Shen, Hangyu Zhang
Journal: Journal of Clinical Oncology (2023)

e16209 Background: Surgical resection is one of the most effective treatments for HCC. However, the recurrence rate after hepatectomy is still very high with the 5-year recurrence rate of 60~70%, which is even higher in patients with high-risk recurrence factors. There is no globally recognized standard adjuvant therapy for HCC after radical resection. Here, we evaluated the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC patients with high risks of recurrence. Methods: We retrospectively analyzed the patients who were diagnosed as hepatocellular carcinoma and underwent R0 resection in Chinese PLA general hospital from June 2021 to Nov 2022, and were confirmed by pathological examination to have any one of the following high-risk factors: the number of tumors ≥ 2, the maximum diameter of tumors ≥ 5cm, portal vein tumor thrombus, microvascular invasion (MVI) and satellite lesions. These patients would receive donafenib combined with anti-PD-1 antibody as adjuvant therapy up to 1 year. The primary endpoint was recurrence free survival (RFS). Secondary endpoints included 1 and 2 year RFS rate, overall survival (OS) and safety. Results: 32 patients were included in this analysis, all of them received donafenib 100mg bid plus anti-PD-1 antibody as adjuvant therapy. Pts were classified as BCLC stage A (50.0%), B (15.6%) and stage C (34.4%). The study population was predominantly HBV-positive (87.5%). 17/32 (53.1%) pts had microvascular invasion, 8/32 (25%) had satellite nodules and 2/32 (6.3%) had portal vein tumor thrombus. 17/32 (53.1%) pts had tumor size ≥5 cm, the median tumor size was 5.00 cm (range 2.0 to 12.5) based on pathological findings and 8/32 (25%) had tumor number≥2. Seven pts (21.9%) underwent secondary surgery after tumor recurrence, the rate of tumor rupture and incomplete capsules were 9.4% and 18.8% respectively. 1 patient (3.1%) had bile duct tumor thrombus. The median duration of follow up was 7.34 months, three pts experienced recurrence and one patient died of liver failure. The 1-year recurrence-free survival rate was 80.1%. The median RFS was 18.62 months (95%CI, 7.33 to 29.91). The median OS was not reached. Among all the pts who received adjuvant therapy, 27 (84.4%) pts had at least one treatment-related AE (TRAE). Grade 3 TRAEs occurred in 4 (12.5%) pts, no grades 4 or 5 were reported. 1 (3.1%) patient discontinued treatment because of high risk of upper gastrointestinal bleeding. Common TRAEs included hand-foot syndrome (28.1%), platelet count decreased (25.0%), aspartate aminotransferase increased (21.9%), rash (18.7%) and blood bilirubin increased (15.6%). Conclusions: The combination of donafenib and anti-PD-1 antibody as adjuvant therapy demonstrated promising efficacy and was well tolerated in HCC patients with high risks of recurrence.